Opioid receptors are members of the receptor superfamily of polypeptides that typically have seven transmembrane domains and that are functionally coupled to G proteins. cDNAs encoding several types of opioid receptors have been cloned, including the mu, delta, and kappa opioid receptors (Wang et al., (1983), Proc. Natl. Acad. Sci., USA, 90:10230; Chen et al., (1993), Mol. Pharmacol., 44:8; Evans et al., (1992), Science, 258:1952; Kieffer et al., Proc. Natl. Acad. Sci., USA, 89:12048; Yasuda et al, (1993), Proc. Natl. Acad. Sci., USA, 90:6736.)
It is believed that the proteins encoded by these cDNAs mediate many of the physiological effects of endogenous opioid agonist peptides, such as, for example, met- and leu-enkephalin, beta-endorphin, and dynorphin, as well as opiate alkaloids such as morphine (Jaffe and Martin, in The Pharmacological Basis of Therapeutics, A. G. Gilman et al., eds., MacMillan, N.Y., 1985, pages 491-531). These physiological effects, which occur in both the central and peripheral nervous system, include analgesia, drowsiness, mood changes, respiratory depression, decreased gastrointestinal mobility, nausea, vomiting, and other alterations in the endocrine and autonomic nervous system.
Another family of opioid receptors, the epsilon receptors, have been studied in brain and immune tissue (Nock et al., (1993), J. Pharm. Expl. Therap., 264:349; Sibinga et al., (1988), Ann. Rev. Immunol., 6:219). Epsilon receptors, in the immune system, appear to mediate the effects of beta-endorphin on the cytotoxicity of monocytes, on conversion of precursor cells into killer cells, and on chemotaxis.
It has been found that some opioid effects may be mediated by receptors other than the known mu, delta, and kappa receptors. This indicates the existence of subtypes of each of these receptor classes. For example, two subtypes of mu-receptor, two subtypes of delta receptor, and three subtypes of kappa receptor have been identified pharmacologically (Pasternak, Clin.Neuropharm. 16:1, 1993).
New opioid receptor polypeptides have now been identified by isolating cDNAs that are homologous to known receptors.